Overview

Also Known As:Acrα7-

These alpha7 nicotinic acetylcholine receptor knockout mice may be useful in studying the cholinergic anti-inflammatory pathway; including inflammatory neurotoxicity in stroke, myocardial infarction, sepsis and Alzheimer's disease, as well as neuropsychiatric diseases such as schizophrenia.

Donating Investigator

Dr. Arthur Beaudet, Baylor College of Medicine

Genetic overview

Genetic Background	Generation
	N10F13 (2021-01-04 00:00:00)

Chrna7^tm1Bay

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Chrna7	cholinergic receptor, nicotinic, alpha polypeptide 7

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Research Applications

Neurobiology Research

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Base Price

Starting at:

$255.00 Domestic price for female 4-week

510.00 Domestic price for breeder pair

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Details

Detailed Description

Mice homozygous for the alpha7 nicotinic acetylcholine receptor null allele (α7 nAChR- or α7-) are viable and fertile. Neuropathological and histochemical assessment of brains from α7 nAChR knockout mice reveal no abnormalities. High-affinity nicotine binding sites are present but there is an absence of high-affinity [I-125] alpha-bungarotoxin sites. Homozygotes lack rapidly desensitizing, methyllycaconitine-sensitive, nicotinic currents that are present in hippocampal neurons.

Development

A null mutation of the alpha7 subunit was prepared by deleting the last three exons (8-10) of the Chrna7 gene. Mice deficient in the alpha 7 subunit were generated by introducing a 7 kb deletion into ES cells. The strain originated on a mixed 129/SvEv and C57BL/6 background. The donating investigator backcrossed these mice to C57BL/6 for approximately eight generations ("N8F8") prior to sending to The Jackson Laboratory.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Orr-Urtreger A; Goldner FM; Saeki M; Lorenzo I; Goldberg L; De Biasi M ; Dani JA ; Patrick JW ; Beaudet AL. 1997. Mice deficient in the alpha7 neuronal nicotinic acetylcholine receptor lack alpha-bungarotoxin binding sites and hippocampal fast nicotinic currents. J Neurosci 17(23):9165-71PubMed: 9364063 MGI: J:44288

View All References

Genetics

Chrna7^tm1Bay

Allele Symbol: Chrna7^tm1Bay

Allele Name	targeted mutation 1, Baylor College of Medicine
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Acralpha7 -; alpha7; alpha7 NNR -; Chrna7^Baytm1
Gene Symbol and Name	Chrna7, cholinergic receptor, nicotinic, alpha polypeptide 7
Gene Synonym(s)
Strain of Origin	129S7/SvEvBrd-Hprt^b-m2
Chromosome	7
Molecular Note	A 7 kb genomic fragment containing exons 8-10 was replaced with a neomycin selection cassette. The deleted sequences encode the second through the fourth transmembrane domains and the cytoplasmic loop. Northern blot analysis on brain samples derived from homozygous mice demonstrated that no detectable transcript was produced from this allele. Western blot analysis on brain extracts derived from homozygous mice also confirmed that no detectable protein was made from this allele.
Mutations Made By	Dr. Arthur Beaudet, Baylor College of Medicine

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

schizophrenia

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Chrna7^tm1Bay related

Neurobiology Research
- Receptor Defects

Neurobiology Research
- Receptor Defects
  - cholinergic receptor
- Channel and Transporter Defects
  - sodium/potassium

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Chrna7^tm1Bay/Chrna7^tm1Bay
involves: 129S7/SvEvBrd * C57BL/6J

reproductive system phenotype

reduced fertility
- homozygotes do not breed well

hematopoietic system phenotype

increased lymphocyte cell number
- increased lymphocytes in bone marrow

decreased erythroblast number
- fewer erythroblasts and pro-normoblasts found in bone marrow

decreased neutrophil cell number
- fewer band neutrophils in bone marrow

abnormal myeloblast morphology/development
- fewer myeloblasts and metamyeloblasts in bone marrow

immune system phenotype

increased lymphocyte cell number
- increased lymphocytes in bone marrow

decreased neutrophil cell number
- fewer band neutrophils in bone marrow

mammalian phenotype

nervous system phenotype
- Normal - homozygotes display normal growth, survival, gait, and anatomy and show no developmental abnormalities in the nervous system

nervous system phenotype

abnormal brain morphology
- Normal - however, autoradiography with [3H]nicotine revealed normal levels of high-affinity nicotine binding
- homozygotes lack high-affinity [125I]alpha-bungarotoxin binding sites

abnormal nicotine-mediated receptor currents
- hippocampal neurons from mutant mice do not exhibit rapidly desensitizing, methyllycaconitine-sensitive nicotinic currents

Genotype: Chrna7^tm1Bay/Chrna7^tm1Bay
involves: 129S7/SvEvBrd * C57BL/6

cellular phenotype

abnormal airway basal cell differentiation
- after polidocanol-induced acute injury, 8-wk old mutant mice display delayed regeneration of the tracheal epithelium with a transient hyperplasia of basal cells observed on days 4 and 6, but not on day 8, after injury

hematopoietic system phenotype

decreased immunoglobulin level
- significantly reduced preimmune serum Ig levels

decreased IgG level

immune system phenotype

decreased IgG level

decreased immunoglobulin level
- significantly reduced preimmune serum Ig levels

mammalian phenotype

immune system phenotype
- Normal - IgM levels of preimmune serum are little altered from control levels

respiratory system phenotype

abnormal airway basal cell differentiation
- after polidocanol-induced acute injury, 8-wk old mutant mice display delayed regeneration of the tracheal epithelium with a transient hyperplasia of basal cells observed on days 4 and 6, but not on day 8, after injury

airway basal cell hyperplasia
- at 1 year of age, the % of 1-2 layers of basal cells in the tracheal epithelium is reduced whereas the % of 3-4 layers of basal cells in increased by 3.8-fold relative to that in wild-type controls

Genotype: Chrna7^tm1Bay/Chrna7^tm1Bay
B6.Cg-Chrna7

homeostasis/metabolism phenotype

abnormal tumor necrosis factor level
- mutant macrophages are refractory to cholinergic agonists and generate TNF normally in the presence of nicotine or acetylcholine
- following endotoxin administration, homozygotes show significantly higher levels of serum TNF levels as well as higher TNF production in the liver and spleen relative to wild-type
- electrical stimulation of the vagus nerve inhibits endotoxin-induced serum TNF levels in wild-type mice, but fails to reduce serum TNF levels in endotoxemic homozygotes

abnormal interleukin level
- endotoxemic homozygotes produce significantly higher levels of IL-1 and IL-6

immune system phenotype

abnormal tumor necrosis factor level
- mutant macrophages are refractory to cholinergic agonists and generate TNF normally in the presence of nicotine or acetylcholine
- electrical stimulation of the vagus nerve inhibits endotoxin-induced serum TNF levels in wild-type mice, but fails to reduce serum TNF levels in endotoxemic homozygotes
- following endotoxin administration, homozygotes show significantly higher levels of serum TNF levels as well as higher TNF production in the liver and spleen relative to wild-type

abnormal interleukin level
- endotoxemic homozygotes produce significantly higher levels of IL-1 and IL-6

mammalian phenotype

behavior/neurological phenotype
- Normal - homozygotes exhibit normal base-line learning and memory performance, and normal sensorimotor gating relative to wild-type
- Normal - significant gender differences are noted in several tests; however, there is no evidence suggesting that these gender differences are genotype-specific
- Normal - also, homozygotes are behaviorally similar to wild-type mice in a wide variety of behavioral tests

nervous system phenotype

abnormal seizure response to pharmacological agent
- homozygotes and wild-type mice display a similar dose-response curve for nicotine-elicited clonic-tonic seizures
- neither cholinergic compensatory mechanisms nor alterations in binding levels or affinity for nicotinic ligands, such as epibatidine or nicotine, can account for the retained sensitivity to the convulsant effects of nicotine

behavior/neurological phenotype

decreased anxiety-related response
- homozygotes spend a significantly greater proportion of their total distance traveled in the open field in the center of the arena relative to wild-type
- however, this difference in altered anxiety-related behavioral response is not corroborated by the light<->dark exploration test

abnormal seizure response to pharmacological agent
- neither cholinergic compensatory mechanisms nor alterations in binding levels or affinity for nicotinic ligands, such as epibatidine or nicotine, can account for the retained sensitivity to the convulsant effects of nicotine
- homozygotes and wild-type mice display a similar dose-response curve for nicotine-elicited clonic-tonic seizures

abnormal spatial learning
- also, homozygotes and wild-type mice show a comparable search behavior during the probe trials
- homozygotes locate the hidden platform in the Morris water task significantly faster than wild-type; however, this is a subtle difference and is not supported by the distance traveled data

Genotype: Chrna7^tm1Bay/Chrna7⁺
involves: 129S7/SvEvBrd * C3H/HeN

taste/olfaction phenotype

impaired olfaction
- mice exhibit deficits in detecting or discriminating chemically-related odors

Genotype: Chrna7^tm1Bay/Chrna7^tm1Bay
involves: 129S7/SvEvBrd * C3H/HeN

taste/olfaction phenotype

impaired olfaction
- mice exhibit deficits in detecting or discriminating chemically-related odors

The following phenotype relates to a compound genotype created using this strain

Genotype: Chrna7^tm1Bay/Chrna7^tm1Bay
B6.129S7-Chrna7/J

behavior/neurological phenotype

abnormal spatial working memory
- Normal - however, mice show normal latency to enter the central zone of the open field, normal elevated plus maze behavior, and no differences in swim speed or thigmotaxic behavior
- in the delayed matching-to-place task of the Morris water maze, mutants take longer to find the hidden platform than controls, indicating a minor impairment in working/episodic memory

nervous system phenotype

abnormal GABAergic neuron physiology
- cortical GABAergic synaptic defects in the prefrontal cortex and in cortical cultures

abnormal cerebral cortex pyramidal cell morphology
- GABAAalpha1 levels are reduced in pyramidal neurons of the prefrontal cortex

abnormal brain interneuron morphology
- GABAAalpha1 levels are reduced in parvalbumin-positive GABAergic interneurons in the prefrontal cortex
- parvalbumin and GAD67 levels are reduced in the soma of parvalbumin-positive GABAergic interneurons
- NMDA receptor expression is reduced in cortical GABAergic interneurons of cortical cultures
- development and maturation of cortical parvalbumin-positive basket cells is impaired in cortical cultures
- development of parvalbumin-positive GABAergic interneurons is disrupted in cortical cultures

decreased CNS synapse formation
- formation of parvalbumin- and GAD65-positive perisomatic synapses is impaired in cortical cultures
- marker analysis indicates that cortical GABAergic synapse formation is impaired in prefrontal cortex and in cortical cultures

abnormal GABAergic neuron morphology
- levels of markers of GABAergic maturation are reduced in the neocortex indicating that cortical parvalbumin GABAergic development is impaired

abnormal cerebral cortex morphology
- cortical levels of GABAergic makers (parvalbumin, glutamic acid decarboxylase 65/67 (GAD65/67) and the alpha1 subunit of GABAA receptors) are decreased during late postnatal development and adulthood

abnormal GABA-mediated receptor currents
- cultured cortical pyramidal neurons show a reduction in sIPSC frequency and current decay time, but not amplitude, indicating reduced GABAergic neurotransmission

reproductive system phenotype

asthenozoospermia
- Normal - however, no significant differences in sperm viability, senescence rate or spontaneous acrosome reaction rate are observed between mutant and wild-type sperm before and after capacitation
- mutant sperm initially appear to swim normally but fail to maintain progressive forward motility
- only few mutant sperm retain rapid swimming velocities and display hyperactivated swimming patterns following in vitro capacitation
- many nonmotile sperm exhibit a quivering head and midpiece but no forward movement, confirming that cells are alive

prolonged estrous cycle
- all female homozygotes eventually complete an estrous cycle, and may achieve pregnancy but with a smaller number of surviving pups
- the extent of asynchrony is variable within the mutant female population, but for a given animal, the average cycle length tends to remain stable at young mature ages (4-6 months) and middle ages (10-14 months)
- female homozygotes show asynchronous, prolonged estrous cycles, with an average cycle length of 7.1 ¿ 0.68 days relative to wild-type and heterozygous females (4.3 ¿ 0.19 and 4.3 ¿ 0.10 days, respectively)

reduced female fertility
- zygous females and homozygous mutant males (7.1 ¿ 0.40)
- the number of live births is significantly less from matings of female homozygotes with either heterozygous (4.5 ¿ 2.12) or homozygous (3.7 ¿ 0.53) mutant males in comparison to matings of heterozygous females and males (7.34 ¿ 0.04) and matings of heterozygous females and homozygous mutant males (7.1 ¿ 0.40)

decreased litter size
- litters born to homozygous mutant females are significantly smaller than those born to heterozygous females regardless of the male genotype

taste/olfaction phenotype

impaired olfaction
- mice exhibit deficits in detecting or discriminating chemically-related odors

cellular phenotype

asthenozoospermia
- mutant sperm initially appear to swim normally but fail to maintain progressive forward motility
- only few mutant sperm retain rapid swimming velocities and display hyperactivated swimming patterns following in vitro capacitation
- Normal - however, no significant differences in sperm viability, senescence rate or spontaneous acrosome reaction rate are observed between mutant and wild-type sperm before and after capacitation
- many nonmotile sperm exhibit a quivering head and midpiece but no forward movement, confirming that cells are alive

mammalian phenotype

reproductive system phenotype
- Normal - testicular weight, total sperm number, and sperm morphology appear normal
- Normal - male homozygotes are fertile and exhibit an apparently normal mating behavior
- Normal - female homozygotes have normal ovaries and enter puberty at the expected age, with no significant differences in the onset of vaginal opening or cornification relative to wild-type or heterozygous control females

Genotype: Chrna7^tm1Bay/Chrna7⁺
B6.129S7-Chrna7/J

taste/olfaction phenotype

impaired olfaction
- mice exhibit deficits in detecting or discriminating chemically-related odors

References

Orr-Urtreger A; Goldner FM; Saeki M; Lorenzo I; Goldberg L; De Biasi M ; Dani JA ; Patrick JW ; Beaudet AL. 1997. Mice deficient in the alpha7 neuronal nicotinic acetylcholine receptor lack alpha-bungarotoxin binding sites and hippocampal fast nicotinic currents. J Neurosci 17(23):9165-71PubMed: 9364063 MGI: J:44288

Additional References

Wang H; Yu M; Ochani M; Amella CA; Tanovic M; Susarla S; Li JH; Wang H; Yang H; Ulloa L; Al-Abed Y; Czura CJ; Tracey KJ. 2003. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421(6921):384-8PubMed: 12508119 MGI: J:89610

Additional - Chrna7^tm1Bay related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Chrna7-Alternate 1
- Standard PCR:Chrna7-Alternate 1
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred to heterozygous mice. Although homozygotes are viable and fertile, the donating investigator reports that breeding is better using heterozygous breeders, and they have observed reduced fertility in homozygotes. Heterozygotes produce small litters. Expected coat color from breeding is Black.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Heterozygote
- Heterozygote x Homozygote
Citation
When using the Acrα7- mouse strain in a publication, please cite the originating article(s) and include JAX stock #003232 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX11 (Maximum)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Breeder Pair

Sex

Genotype

Price

Female
Male

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Chrna7<tm1Bay>

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:Acrα7-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Chrna7tm1Bay

Allele Symbol: Chrna7tm1Bay

Disease Terms

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Chrna7tm1Bay related

Mammalian Phenotype Terms by Genotype

Genotype: Chrna7tm1Bay/Chrna7tm1Bayinvolves: 129S7/SvEvBrd * C57BL/6J

reproductive system phenotype

hematopoietic system phenotype

immune system phenotype

mammalian phenotype

nervous system phenotype

Genotype: Chrna7tm1Bay/Chrna7tm1Bayinvolves: 129S7/SvEvBrd * C57BL/6

cellular phenotype

hematopoietic system phenotype

immune system phenotype

mammalian phenotype

respiratory system phenotype

Genotype: Chrna7tm1Bay/Chrna7tm1BayB6.Cg-Chrna7

homeostasis/metabolism phenotype

immune system phenotype

mammalian phenotype

nervous system phenotype

behavior/neurological phenotype

Genotype: Chrna7tm1Bay/Chrna7+involves: 129S7/SvEvBrd * C3H/HeN

taste/olfaction phenotype

Genotype: Chrna7tm1Bay/Chrna7tm1Bayinvolves: 129S7/SvEvBrd * C3H/HeN

taste/olfaction phenotype

Genotype: Chrna7tm1Bay/Chrna7tm1BayB6.129S7-Chrna7/J

behavior/neurological phenotype

nervous system phenotype

reproductive system phenotype

taste/olfaction phenotype

cellular phenotype

mammalian phenotype

Genotype: Chrna7tm1Bay/Chrna7+B6.129S7-Chrna7/J

taste/olfaction phenotype

References

Additional References

Additional - Chrna7tm1Bay related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Breeder Pair

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Chrna7^tm1Bay

Allele Symbol: Chrna7^tm1Bay

Genotype: Chrna7^tm1Bay related

Genotype: Chrna7^tm1Bay/Chrna7^tm1Bay
involves: 129S7/SvEvBrd * C57BL/6J

Genotype: Chrna7^tm1Bay/Chrna7^tm1Bay
involves: 129S7/SvEvBrd * C57BL/6

Genotype: Chrna7^tm1Bay/Chrna7^tm1Bay
B6.Cg-Chrna7

Genotype: Chrna7^tm1Bay/Chrna7⁺
involves: 129S7/SvEvBrd * C3H/HeN

Genotype: Chrna7^tm1Bay/Chrna7^tm1Bay
involves: 129S7/SvEvBrd * C3H/HeN

Genotype: Chrna7^tm1Bay/Chrna7^tm1Bay
B6.129S7-Chrna7/J

Genotype: Chrna7^tm1Bay/Chrna7⁺
B6.129S7-Chrna7/J

Additional - Chrna7^tm1Bay related